Genomic DNAs from a variety neoplastic and normal tissues were analyzed by transfectional analysis for the presence of activated cellular oncogenes. Despite reports to the contrary, normal tissues from patients with many primary tumors and/or strikingly positive family histories did not exhibit oncogene activation. A variety of human tumors were found where a small minority were positive (e.g., 1/7 sarcomas, 1/14 Hodgkin's lymphomas, and 1/22 chronic myelogenous leukemias (CML). However, two tumors, human acute myelogenous leukemia (AML), and dimethyl-nitrosamine (DMN)-induced renal sarcoma were positive in a much higher percentage of tumors (3/6 AML and 5/5 renal sarcomas). Efforts were thus directed at these two tumors. In the case of AML, transforming capacity is asociated with acquisition of human c-N-ras, and the gene product, p21, appears to have the same aberrant mobility in each patient. Patients whose tumor DNA is positive in transfection appear to be younger and have larger, more massive tumor burdens. Further studies are needed to confirm these preliminary observations. In DMN-induced renal sarcomas, transformation of 3T3 cells is associated with acquisition of rat c-ras-K. This is of interest in that nitrosomethylurea, which is metabolized to the same active metabolite as DMN, causes breast cancer when given IV to rats in association with c-ras-H activation.